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Role of Gas6 in erythropoiesis and anemia in mice

Angelillo-Scherrer, Anne
Lambrechts, Diether
Tjwa, Marc
Plaisance, Stéphane
Sugamele, Rocco
DeMol, Maria
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Published in Journal of Clinical Investigation. 2008, vol. 118, no. 2, p. 583-596
Abstract Many patients with anemia fail to respond to treatment with erythropoietin (Epo), a commonly used hormone that stimulates erythroid progenitor production and maturation by human BM or by murine spleen. The protein product of growth arrest-specific gene 6 (Gas6) is important for cell survival across several cell types, but its precise physiological role remains largely enigmatic. Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. In the absence of Gas6, erythroid progenitors and erythroblasts were hyporesponsive to the survival activity of Epo and failed to restore hematocrit levels in response to anemia. In addition, Gas6 may influence erythropoiesis via paracrine erythroblast-independent mechanisms involving macrophages. When mice with acute anemia were treated with Gas6, the protein normalized hematocrit levels without causing undesired erythrocytosis. In a transgenic mouse model of chronic anemia caused by insufficient Epo production, Gas6 synergized with Epo in restoring hematocrit levels. These findings may have implications for the treatment of patients with anemia who fail to adequately respond to Epo.
Keywords Anemia/drug therapy/geneticsAnimalsCell Adhesion/geneticsCell SurvivalDisease Models, AnimalDrug ResistanceErythroblasts/drug effects/metabolismErythropoiesis/geneticsErythropoietin/genetics/pharmacology/therapeutic useHumansIntercellular Signaling Peptides and Proteins/genetics/metabolism/therapeutic useMiceMice, Mutant StrainsOncogene Proteins/genetics/metabolismProto-Oncogene Proteins/metabolismProto-Oncogene Proteins c-akt/metabolismReceptor Protein-Tyrosine Kinases/genetics/metabolismReceptors, Erythropoietin/agonistsRecombinant Proteins/genetics/pharmacology/therapeutic use
PMID: 18188450
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Research groups Endothélium vasculaire (11)
Lupus érythémateux systémique, de l'anémie hémolytique et de la glomérulonéphrite (168)
Mucoviscidose et jonctions GAP (229)
Recherche translationnelle : anomalies de l'hémostase et thromboses (504)
(ISO format)
ANGELILLO-SCHERRER, Anne et al. Role of Gas6 in erythropoiesis and anemia in mice. In: The Journal of clinical investigation, 2008, vol. 118, n° 2, p. 583-596. doi: 10.1172/JCI30375 https://archive-ouverte.unige.ch/unige:2105

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Deposited on : 2009-06-19

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